10EX
CIT
ING
CA N C E R RE
SE
AR
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EX
CIT
ING
CA N C E R RE
SE
AR
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SIN C E 2 0 02
SIN C E 2 0 02
YEARS OFYEARS OF
GSC neurosphere in vitroPseudopallisadingnecrosis in GBM
MRI scan of a GBM
PROLIFERATION
INVASION
METABOLISM
ANGIOGENESIS
Glioblastoma cell
Extracellular matrix BAI1
8, 3028
4
28
27, 43
4
29, 34
1, 25 55
5427, 43
20
20
1, 25
10, 17, 19, 45
8, 30 5, 9, 14
THBS1 VEGF
MET, EGFR, PDGFR
MET
MAPK
TRKA
PGK1GLUT1VEGF
mTOR
DNAdamage
mTOR
RAS PI3K
AKT
NF1
PTEN
MAPKpathway
S-phasegenes
ARF/MDM2/p53
RBINK4A
Aberrantmetabolism
HIF1a
MYC p53
PHD
D-2-HG
Histone demethylases
G-CIMP phenotype
TET family
a-KG
a-KG
b-oxidation
IDH2Acetyl-CoA
Fatty acids
Pyruvate
GlucoseGlycolysis
Fatty acid synthesisIsocitrate
CitrateMut IDH1IDH1
NADPH
NADPH
NADP+
NADP+Glutamate
GlutamineGLS
GSH
Reactive oxygen species
Mutation
GAB1
SHP2
GRB2/SOS
NF1RAS
RAF
MIRK (DYRK1B)
RANBPM(RANBP9)
ZEB1
E-cadherinuPAMMPs Migration, Invasion
ITGB1
TRAF6
IkB
Apoptosis
Proliferation
p53 Hypoxia PI3K pathway, Mut IDH1
HIF1a
SCF PIGF ANGPT1/2 BFGF PDGF
aVb5
NF-kB
CD36,aVb3aVb5
VEGFR2 KIT PIGFR
MAPK & PI3K pathways
EC division, vascular permeability, EC migration, mobilization of BM-EPCs
TIE2 FGFR PDGFRNotchEndothelial cell
GLIOMA STEM CELLSNormal differentiation pathway Gliomagenesis Clonal evolution model
Notch
OligodendrocyteNeuron Progenitor
cell
Astrocyte Astrocytoma
Oligodendroglioma
OA mixed
NSC
Notch, SHH/GLI, STAT3
GSC
Cell cyclearrest
CTGFHGF (SF)
Krebscycle
Nucleus
Mitochondria
(5mC-Hydroxylases)
Brain whole mount with GBMTumor massTumor mass
MicrovascularproliferationMicrovascularproliferation
Invadingcells
InvadingcellsHypoxiaHypoxia
CTGFCTGF
ReactiveastrocytesReactive
astrocytes
DLL
#123456789101112131415161718192021222324252627282930313233
35
37
39
41
43
45
47
49
51
34
36
38
40
42
44
46
48
50
52535455
RilotumumabAfliberceptAfatimibBevacizumabBrivanibCediranibCetuximabCilengtideLenvatinib mesylateEnzastaurinErlotinibGefitinibImatinibIntedanibLapatinibBKM120NelfinavirPazopanibPerifosineSorafenibSunitinibTandutinibTemsirolimusVandetanibCabozantinibXL765TipifarnibR04929097VeliparibATN-161AZD8055AZD2014BKM120
Rindopepimut
Matuzumab
Foretinib
Olavatumab
Lonafarnib
MK2206
Dacomitinib
Panobinostat
Sirolimus
Iniparib
Pegdinetanib
Everolimus
Ramucirumab
I-125 MAB-425
ABT-806
Nimotuzumab
PX-866
Ridaforolimus
VatalanibXL147BortezomibAZD7451
DRUG
3, 7, 11, 12, 15, 24, 25, 35, 37, 42, 44, 46, 47
6, 9, 13, 14, 18, 20, 21, 22, 41, 52
2, 5, 6, 9, 14, 18, 20, 21, 24, 25, 36, 39, 40, 52
6, 13, 18, 20, 21, 22, 25
23, 26, 31, 32, 38, 50, 51
10, 16, 26, 33, 48, 53
These pharmacological agents affect targets shown in red.
SnapShot: Glioblastoma MultiformeSvetlana Kotliarova and Howard A. FineCenter for Cancer Research, National Cancer Institute, National Institutes for Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
See o
nline version fo
r legend
and references.
710 C
ancer Cell 21, M
ay 15, 2012 ©2012 E
lsevier Inc. D
OI 10.1016/j.ccr.2012.04.031
Culture brain tumor stem cells (BTSCs) with NeuroCult™ NS-A (Catalog #05751):
SPECIALIZED. Formulated to maintain human neural stem cells and BTSCs in long-term culture.
VERSATILE. Supports isolation and proliferation of BTSCs from a variety of tumor types, using either neurosphere or monolayer culture techniques.
CONSISTENT. Conforms to STEMCELL Technologies’ stringent quality control standards, including rigorous performance testing using primary cells.
STEMCELL Technologies is committed to making sure your research works. As Scientists Helping Scientists, we support our customers by creating novel products with consistent un-failing quality and by providing unparalleled technical support.
Identify and isolate viable BTSCs:
NeuroFluor™ CDr3 (Catalog #01800) for detection and isolation of BTSCs based on FABP7 expression (Yun et al., PNAS 2012).
ALDEFLUOR™ (Catalog #01700) for detection and isolation of BTSCs based on aldehyde dehydrogenase (ALDH) enzyme activity.
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